GENERAL PHARMACOLOGY

NOMENCLATURE

Pharmacology deals with the knowledge of drugs. Drugs are chemical substances which affect living organisms and are used
by the clinician to diagnose, prevent or cure diseases. So the safe use of drugs needs sound knowledge of their various
aspects such as mechanism of action, doses, routes of administration, adverse affects, toxicity, drug interactions etc. A health
professional is also interested to know the chemical agents that are commonly responsible for household and industrial
poisoning as well as environmental pollution so that he may prevent, recognize and treat such toxicity or pollution.

The word pharmacology is derived from the Greek words pharmakon (drug) and logos (study). The word drug has also a
French origin-- 'drouge' (dry herb). In clinical practice, drug is a chemical substance that is used for the diagnosis, prevention
and treatment of diseases in appropriate doses. WHO (1966) definition of a drug is any substance or product that is used or
intended to be used to modify or to explore physiological system or pathological states for the benefit of the recipient.

Following are the major subdivisions of pharmacology:

• Pharmacy is a branch of pharmacology that deals with identification, selection, preservation, combining, analyzing,
standardization, preparing, compounding and dispensing of medicines for administration to the patient. A pharmacist
prepares compounds and dispenses medicines to the patient upon a written order of a licensed medical practitioner.

• Pharmacognosy is a term derived from the Greek word 'gnosis' which means knowledge. It is a branch of
pharmacology that deals with the sources of drugs derived from plants and animals. It is also a study of physical and
chemical properties of such substances.

• Pharmacokinetics is a term derived from the Greek word 'kinesis' meaning a movement. It deals with the time
course of drug absorption, distribution, metabolism and excretion. In other words, it means "What the body does to
the drug". It provides a rational basis for doses of a drug and helps in dosage adjustment in altered physiological and
pathological states like aging, renal or hepatic impairment.

• Pharmacodynamics (Greek 'dynamics' means force) is the study of physiological and biochemical effects of drugs,
mechanisms of action and the relationship of the plasma concentration of the drug with its response and the duration
of action. In other words, it means "What the drug does to the body".

• Pharmacotherapeutics (Greek 'therapia' means medical treatment) deals with the use of drugs in the diagnosis,
treatment or prevention of a disease or their purposeful use in alteration of physiological functions for the benefit of
the recipient. In other words, it is the clinical application of the pharmacokinetic and pharmacodynamic knowledge of
the drug.

• Therapeutics deals with the science and art of treatment of diseases. When therapy is based on clinical evidence it
is called Empirical Therapeutics. It means the drug is effective, although its mode of action is unknown.

• Chemotherapy deals with the use of chemotherapeutic agents to inhibit or destroy invading microbes, parasites or
cancer cells with minimal effect on healthy living tissues.

• Toxicology (Greek 'toxicon' means poison) is the science of poisons. It deals with the adverse effects of drugs and
poisonous effects of various chemicals (household, environmental, industrial or homicidal). It is also concerned with
their source, chemical composition, action, tests for detection and antidotes.. Clinical toxicology is the science of
detection, diagnosis and treatment of poisoning.

• Pharmacogenetics is a relatively new field. It deals with genetically mediated variations in drug responses.

• Clinical Pharmacology is a branch of pharmacology that deals with the pharmacological effects of drugs in man. It
gives useful data about the potency, usefulness, doses and toxicity of new drugs for their safe clinical use.

• Biopharmaceutics deals with the development of new drug delivery systems and new dosage forms. It also
provides information how these dosage forms can influence the pharmacodynamic and pharmacokinetic properties of
a drug.

• Medicinal Chemistry is the science of designing and synthesis of a new drug. It is based on the structure activity
relationship data of existing drugs belonging to one generic group.
DRUG INFORMATION SOURCES

Most useful drug information sources are textbooks, drug reference books, drug compendia and journal articles. They provide
information about established drugs and furnish information for understanding newer ones. However, they do not include
many other details such as trade names, physical and chemical properties, identification criteria, standards of purity and
strength, methods of storage and dosage range for therapeutic use which are necessary from a legal point of view for drug
control. All these details of drugs are provided by Pharmacopoeias and Formulary. They are collectively known as Drug
Compendia. Pharmacopoeias are prepared by a committee, which usually has predominance of physicians. Formulary is
prepared by a committee, which usually has predominance of pharmacists. Then there are non-official sources of information.

Pharmacopoeia: It is an official code containing a selected list of the established drugs and medicinal preparations with
descriptions of their physical properties, identification, purity, potency and the minimum standard required and the average
dose for adults. Each country has its own pharmacopeia. For example:

• British Pharmacopeia
• United States Pharmacopeia
• Indian Pharmacopeia
• European Pharmacopeia
• Russian Pharmacopeia
• International Pharmacopeia

2. Formulary: It includes information on drugs, other pharmaceutical products and formulated products in the respective
countries.

• British National Formulary is published by the British Medical Association

• National Formulary is published by American Pharmaceutical Association.
• National Formulary of India is published by the Government of India.

Non- Official Compendia

They are secondary sources of drug information which give useful and miscellaneous information about drugs for
pharmacists and medical practitioners. They include both generic and trade names of the drugs. The information is not limited
to drugs which are approved for use by legally constituted committee of that country. Some examples of non-official
compendia are:

1. AMA Drug Evaluation: by American Medical Association

2. Drug Information for the Health Care Profession: by United States Pharmacopeial Convention Inc. Maryland, USA
3. Modern Drug Encyclopedia: by Yorke Medical Books, New York, U.S.A.
4. Martindale Extra Pharmacopeia: by Pharmaceutical Society of Great Britain
5. Physicians' Desk Reference (PDR): by Medical Economies Publication, U.S.A.
6. Remington's Pharmaceutical Science: by Mack Publishing Company, U.S.A.
7. United States Dispensary (USD): by Lippincot Publications, U.S.A.

BRIEF HISTORY OF PHARMACOLOGY

Since the dawn of civilization, herbal drugs and other natural source materials have been used for the alleviation of human
suffering. "Traditional" systems of medicine were developed by all civilizations. Pan Tsao is the great herbal "materia medica"
of China. Sken Ming probably wrote it in 2735 B.C. It contained many vegetable and mineral preparations as well as a few
animal products.

Ayurveda contains the earliest Indian records of "traditional"medicine. It dates back to 2500 BC. "Dravyaguna" is the first
Ayurvedic "materia medica". It includes sources, descriptions, criteria for identification, properties, methods of preparation
and therapeutic uses of hundreds of medicinal herbs. Eber's Papyrus is the first written account of medical experiences from
Egypt. It contains more than 700 prescriptions including castor-oil and tincture opii. Hippocrates (a Greek physician of 5th
century B.C.) is known as the Father of Modern Medicine, because he organized the science of medicine on the basis of
analysis, observations and deductions. Theophrastus (300 BC) is called the Father of Pharmacology because of his accurate
observations of medicinal plants.
Galen, a Greek pharmacist physician (131-201 AD), introduced the concept of polypharmacy. He wrote 200 books which
included preparations of crude vegetable drugs. His name is retained in the term "galanical" pharmacy. Paracelsus (1493-
1541 AD) criticized the Galenic system of polypharmacy and introduced the use of simple chemicals for treating diseases
such as mercurials in the treatment of syphilis. Pharmacology is a relatively recent branch of medical science. In fact,
pharmacology originated as a branch of Physiology. Early half of the 19th century was the era of heroic medicine. Samuel
Haneman stressed the need of scientific foundation to therapeutics. He wrote the first edition of his book "Pharmacologia Sen
Manuchitio ad Materiam Medicam" which gave birth to the discipline of Pharmacology.

The first independent pharmacological laboratory was set up at Dorpat in 1849 by Rudolf Buchhem in the German University.
However, Oswald Schmiedeberg (1838-1921) is considered the Father of Pharmacology because he became the first
University Professor of Pharmacology at Strausbergin 1872. He attracted a large number of enthusiastic workers to his
laboratory and many of them became prominent pharmacologists later on such as John Jacob Abel (1857-1938) of the
U.S.A. and Arthur Robertson Cushney (1866-1926) of the U.K. Other important pharmacologists in the U.K. were Thomas
Richard Fraser, Alfred Joseph Clark and Henry Dale.

In India, Col. Sir Ram Nath Chopra((1882-1973) initiated, promoted and established pharmacology as a teaching and
research discipline. He was the first to be appointed as Professor of Pharmacology (1921) in the newly established Calcutta
School of Tropical Medicine and was simultaneously head of the Department of Pharmacology at the Calcutta Medical
College. He is known as the Father of Pharmacology in India.

SOURCES & NATURE OF DRUGS

Drug is a substance which is used for the following purposes:

• Diagnosis of the disease

• Prevention of the disease
• Treatment or palliation (relief of symptoms) of disease
• Prevention of pregnancy (i.e. contraception)
• Maintenance of optimal health

Sources of drugs are as follows:

I. SYNTHETIC SOURCES

At present majority of drugs used in clinical practice are prepared synthetically, such as aspirin, oral antidiabetics,
antihistamines, amphetamine, chloroquine, chlorpromazine, general and local anaesthetics, paracetamol, phenytoin,
synthetic corticosteroids, sulphonamides and thiazide diuretics.
Advantages of synthetic drugs are:

• They are chemically pure.

• The process of preparing them is easier and cheaper.
• Control on the quality of the drug is excellent.
• Since the pharmacological activity of a drug depends on its chemical structure and physical properties, more effective
and safer drugs can be prepared by modifying the chemical structure of the prototype drug.

II. NATURAL SOURCES

Drugs are obtained from the following natural sources:

A- PLANTS:

Following categories of drugs are derived from roots, leaves or barks of plants:

a) Alkaloids

• These are nitrogenous heterocyclic bases, which are pharmacologically active principles of plants.
 • They are composed of carbon, hydrogen, nitrogen and oxygen.
• They are bitter in taste and are often poisonous. These are, therefore, used in small doses.
• They are insoluble in water. However, they form salts with acids which are soluble in water.

Some examples of alkaloids and their sources are listed in the table:

ALKALOID SOURCE
Atropine Atropa belladonna
Quinine Cinchona bark
Morphine Papavarum somniferum
Reserpine Rauwolfia serpentina
Nicotine Tobacco
Digoxin Digitalis lanata
Caffeine Coffee, Tea, Cocoa

b) Glycosides

• They are ether-like combination of sugar moiety with non-sugar moiety.

• They are called glucosides, if the sugar moiety is glucose.
• Sugar moiety is not essential for the pharmacological activity but it governs the pharmacokinetic properties of the
glycoside. In the body it may be removed to liberate aglycone.
• Pharmacological activity resides in the non-sugar moiety that is called aglycone (or genin).
• Some examples are digitoxin, digoxin and ouabain.

c) Oils . They are liquids which are insoluble in water. They are of three types and are used for various medicinal purposes.

i) Essential Oils (or volatile oils): Essential oils are obtained from leaves or flower petals by steam distillation, and have an
aroma.

• They have no caloric or food value.

• They do not form soaps with alkalies.
• They do not leave greasy stain after evaporation.
• On prolonged stay, they do not become rancid (foul smell).
• They are frequently used as carminatives and astringents in mouth-washes.
• Some of these oils are solid at room temperature and sublime on heating e.g. menthol and camphor.
• Other examples are clove oil, peppermint oil, eucalyptus oil and ginger oil.

ii) Fixed oils are glycerides of stearic, oleic and palmitic acid.

• They are obtained from the seeds that are present within the cells as crystals or droplets.
• They are non-volatile and leave greasy stains on evaporation.
• They have caloric or food value.
• They form soaps with alkalies.
• On prolonged stay, they become rancid.
• They do not have marked pharmacological activity and have little pharmacological use except castor
oil (purgative) or arachis oil (demulcent).
• They may be of vegetable origin e.g. olive oil, castor oil, croton oil and peanut oil or of animal origin
e.g. cod liver oil, shark liver oil and lard .

iii) Mineral Oils are mostly petroleum products and extracted by fractional distillation.

• These are mixtures of hydrocarbons of the methane and related aliphatic series.
• These are extracted in various consistencies - hard paraffin, soft paraffin and liquid paraffin.
• Hard and soft paraffins are used as vehicles for preparation of ointments while liquid paraffin is
employed as a purgative.
d) Gums are colloidal exudates from plants which are polysaccharides chemically and yield simple sugars on hydrolysis.

• Upon addition of water, some of them swell or dissolve or form adhesive mucilage or remain unchanged.
• Uses: - In gut agar and psyllium seeds act as hydrophilic colloids and function as bulk purgatives.
• Gum acacia and gum tragacanth are used as suspending agents in making emulsions and mixtures.

e) Resins are ill-defined solid substances found in plants, and are polymers of volatile oil.

• They are produced by oxidation and polymerization of volatile oils.

• They are insoluble in water but soluble in alcohol, chloroform and ether.
• Examples: oleoresins (aspidium); gum resins (asafoetida); oleogum resin (myrrh); balsams (benzoin, tolu,
peru); benzoin shellac, podophyllum.
• Uses:
o Benzoin is used as inhalation in common cold.
o Tincture benzoin is applied as antiseptic protective sealing over bruises.
o Colophony (an oleoresin) is used as an ingredient in various plasters.
o Shellac (from Lucifer lacca) is used for enteric coating of tablets.
o Balsams are used in the treatment of cough and bronchitis for their antiseptic and protective
properties.
o Podophyllum is used as an irritant purgative.

f) Tannins are non-nitrogenous phenolic plant constituents which have an astringent action.

• Pyrogallol tannins are glycosides of glucose that occur in oak galls.

• Pyrocatechol tannins are sugar-free derivatives of catechol that are present in catechu and eucalyptus.
• Tannic acid is a tannin that is obtained from oak galls and is used for treating burns and diarrhoea.

B-ANIMAL SOURCES

Some animal sources continue to be used to procure some modern drugs because of cumbersome and expensive
procedures for the synthesis of such chemicals. For example:

• Insulin, extracted from pork and beef pancreas, is used for the treatment of diabetes mellitus.
• Thyroid powder for treating hypothyroidism.
• Heparin is used as an anticoagulant.
• Hormones and vitamins are used as replacement therapy.
• Vaccines (cholera, T.B., smallpox, polio and antirabic) and sera (antidiptheria and antitetanus) are used for
prophylaxis/treatment.

C-MICROBIOLOGICAL SOURCES

Many life-saving drugs are obtained from fungi, moulds and bacteria e.g. penicillin from Penicillium notatum, chloramphenicol
from Streptomyces venezuelae, grisofulvin (an anti-fungal drug) from Penicillium griseofulvum, neomycin from Streptomyces
fradiae and streptomycin from Streptomyces griseus.

D-MINERAL SOURCES

Minerals or their salts are useful pharmacotherapeutic agents. For example:

• Ferrous sulfate is used in iron deficiency anaemia.

• Magnesium sulfate is employed as purgative.
• Magnesium trisilicate, aluminium hydroxide and sodium bicarbonate are used as antacids for hyperacidity and peptic
ulcer.
• Kaolin (aluminium silicate) is used as adsorbent in antidiarrheal mixtures.
• Radioactive isotopes of iodine, phosphorus, gold are employed for the diagnosis/ treatment of diseases particularly
malignant conditions.
III. SEMISYNTHETIC SOURCES

Sometimes semi-synthetic processes are used to prepare drugs when the synthesis of drugs (complex molecules) may be
difficult, expensive and uneconomical or when the natural sources may yield impure compounds. Some examples are
semisynthetic human insulin and 6-aminopenicillanic acid derivatives.

IV. BIOSYNTHETIC SOURCES (genetically engineered drugs)

This is relatively a new field which is being developed by mixing discoveries from molecular biology, recombinant DNA
technology, DNA alteration, gene splicing, immunology and immunopharmacology. Some of the recent developments are
genetically engineered novel vaccines (Recombinex HB - a hepatitis-B vaccine), recombinant DNA engineered insulins
(Humulin- human insulin) for diabetes and interferon-alpha-2a and interferon-alpha-2b for hairy cell leukaemia.

DRUG NOMENCLATURE

Three types of names are assigned to every drug.

g) CHEMICAL NAME: This name is given according to the chemical constitution of a drug. It indicates the precise
arrangement of atoms and atomic groups in the molecule. However, chemical names are too complex and cumbersome to be
used in prescription.

h) NON-PROPRIETARY /GENERIC NAME: When a drug has been found therapeutically useful, it is given a non-proprietary
name by the United States Adopted Name (USAN) council. These names are used uniformly all over the world by an
international agreement through the W.H.O. Non-proprietary name is called official when included in official books such as
Indian, British, United States or International pharmacopeia. The non-proprietary name is often referred to as generic name.

i) PROPRIETARY /TRADE/BRAND NAME: The pharmaceutical company, which sells the non-proprietary drug selects the
proprietary name and gets it registered. The trade name then becomes the sole property of the pharmaceutical company.
Thus a non-proprietary drug may be marketed under many proprietary names by different firms. Proprietary name is usually
smaller than the non-proprietary name and it is most widely used by medical practitioners.
Some examples are:

Chemical Name Non-Proprietary Name Proprietary Name

-1-(4-chlorobenzenesulphonyl-3-
Chlorpropamide Diabinese ®Copamide ® (Dey's)
propylurea)
-chlorodihydromethyl-phenyl Valium ® (Roche, India)Calmpose ® (Ranbaxy,
Diazepam
benzodiazepine-2-one India)

® is suffixed on the trade name indicating registered name.

Prototype Drug:

Usually, attention is focused on one or at the most two drugs belonging to a group in order to comprehend and co-relate their
pharmacological effects with the other drugs of the same group. . Drugs selected for this purpose are called prototype drugs
e.g. chlorpromazine is a prototype drug for anti-psychotic drugs and morphine is a prototypal drug for narcotic analgesics.

CATEGORIES OF DRUGS:

Drugs may be divided into two categories:

A) Prescription Drugs: These drugs are used under medical supervision because these are considered to be unsafe. So they
are dispensed only by an order of registered physician. e.g. antibiotics, anxiolytics, antidepressant etc.

B) Non-Prescription Drugs: These drugs are considered relatively safe and can be sold without physician's prescription over
the counter (OTC ) e.g. vitamins, antacids, paracetamol etc.